ORIGINAL ARTICLE

Survey of the treatment of Chlamydia trachomatis infection of the female genital tract PREBENAAVITSLAND From the Department of Infectious Disease Control, National Institute of Public Health, Oslo, Norway

Acta Obstet Gynecol Scand 1992; 71: 35&360

A questionnaire was sent to every tenth ( n = 302) general practitioner in Norway. The physicians were to indicate their choice of antibiotic regimen for the treatment of genital chlamydial infections in women. Sixty-nine percent of the practitioners responded. The choice of treatment varied widely between the respondents. Forty-two different regimens were used for chlamydial cervicitis, 34 for cervicitis in pregnancy and 63 for probable pelvic infection. Of the prescribed treatments for these three diagnoses 14%, 5% and 46%, respectively, were compatible with the advice of the World Health Organization or the Centers for Disease Control. For the three previously mentioned diagnoses 49%, 79% and 43%, respectively, of the practioners would prescribe an antibiotic in either smaller doses, fewer daily doses or shorter duration than recommended. There is an urgent need to improve and standardize Norwegian general practitioners’ treatment of chlamydial infection in women. Key words: chlamydia trachomatis; treatment; survey; general practitioners Submitted November 26, 1991 Accepted March 16, 1992

Norway is experiencing an epidemic of genital chlamydial infection. More than 12,000 cases were reported both in 1989 and in 1990 (1) and the same number of cases are expected in 1991 (2). Genital chlamydial infections will be included in the new Communicable Diseases Act in Norway, thus making the treatment free of charge. It would, therefore, be of interest to survey what kind of antibiotic regimens are being used to treat these infections. The manufacturers of antibiotics publish their own guidelines for treatment of chlamydial infections ( 3 ) , but no official recommendations exist. Various international organizations have recommended several regimens for the treatment of uncomplicated chlamydial cervicitis (Table I). For complicated infections (i.e. endometritis, parametritis, salpingitis) the same regimens are extended from 7 to 10 ( 5 ) or 1G14 days (4). Some authorities (6), however, advocate that all cases of cervicitis be Acta Obstet Gynecol Scand 71 (LYY2)

treated as complicated; claiming that one cannot clinically distinguish between an uncomplicated and a complicated case. Considerable variation in the treatments prescribed for chlamydial infection of the cervix (7) was found in a survey of the genitourinary medicine clinics in the UK. In Norway there are only 3 genitourinary medicine clinics. Hence, most cases of genital chlamydial infection are treated by general practitioners (GPs). This survey was designed to assess how genital chlamydial infections in women are treated by Norwegian GPs.

Materials and methods A questionnare was sent to every tenth (n = 302) G P on the alphabetical membership roll of the Norwe-

Treatment of chlamydial infection

351

Table I. Recommended regimens for the treatment of uncomplicated endocervical or urethral infections with Chlamydia trachomatis ~~

Regimen

Recommended by*

Cost in Norway**

Doxycycline, 100 mg 2/day for 7 days Tetracycline 500 mg Wday for 7 days Erythromycin 500 mg 4/day for 7 days Sulfisoxazole****, 500 mg 4/day for 10 days Sulfafurazole****, 500 mg 4/day for 7 days Lymecycline, 300 mg 2/day for 7 days

CDC, WHO, Uppsala CDC, WHO, Uppsala*** CDC, WHO, Uppsala

f14 f 5.1 216 not available not available f 7.6

CDC WHO Uppsala ~

*CDC = Centers for Disease Control (4). WHO = World Health Organization ( 5 ) , Uppsala Center for Sexually Transmitted Diseases and Their Complications, Uppsala (6) **Cheapest alternative. Standard retail price ***Uppsala recommends 500 mg 2/day for 10 days ****Orequivalent sulfonamid

gian Medical Association, with a follow-up two weeks later. The GPs were to indicate which antibiotic regimen they would prescribe to a woman with the following chlamydial infections:

=

WHO Collaborating

Results Two hundred and twelve questionnaires were returned. Eleven of these were unanswered because the physician was either abroad o r no longer practicing. Of the remaining 201 (69%), a number of the GPs did not answer all the questions. Doxycycline and lymecycline were the antibiotics most frequently used for treatment of non-pregnant patients with genital chlamydial infection, while erythromycin was the antibiotic most frequently used for pregnant patients (Table 11). There was a considerable variation in the prescribed regimens of all the antibiotics. Seven GPs ( 5 % ) would treat cervicitis in pregnancy with tetracyclines. No regimen was used by more than a quarter of the GPs (Table 111). The most frequently used regimens for treatment of cervical infection and cervical infection in pregnancy were less (i,e.: smaller doses, fewer daily doses o r shorter duration) than those recommended. Eight out of ten GPs would treat chlamydial cervicitis in pregnancy with an antibiotic regimen that is

A . Cervicitis B. Cervicitis in pregnancy (14 weeks) C. Probable pelvic infection (lower abdominal tenderness, bilateral adnexal tenderness, uterine motion tenderness and an elevated erythrocyte sedimentation rate (35mm/h), but in an otherwise normal general condition (8)). The GPs also indicated their own background information (sex, number of years since graduation, the number of chlamydia-patients diagnosed per month, and the number of patients between the ages of 15 and 30 years seen per month). The responses were registered and analyzed in the WHOKDC EpiInfo software, and a logistic regression performed in SPSS/PC+.

Table 11. Antibiotics used in the treatment of genital chlamydial infection Antibiotic

Cervical infection GPs using No.

Doxycycline Lymecycline (Oxy-)tetracycline Erythromycin Cotrimaxole Other Total

100 63 14 4 3 1 185

No. of different regimens YO

54 34

8 2 2 1 101

16 8 10 4 3 1 42

Cervical infection No. of in pregnancy different regimens GPs using No. Yo

7 0

5

0

0 92 2 1 100

139 3 2 151

0

5 0 0 24 3 2 34

Probable pelvic infection GPs using No.

Yo

102 50 12 7 3 1 175

58 29 7 4 2 1 101

No. of different regimens

31 12 11 6 2 1 63"

*Of which 19 (30%) includes another drug 25

Actu Obstet Gynecol Scund 71 (1992)

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P. Aavitsland

Table 111. Regimens most often used in the treatment of genital chlamydial infection GPs using No.

Regimen

O/O

Cervical infection

Doxycycline 200 mg start, then 100 mg for 9 days Lymecycline 300 mg 2/day for 10 days Lymecycline 300 mg 2/day for 7 days Doxycyclinc 100 mg 2/day for 10 days Other regimens Total

185

22 16 Y 8 45 100

39

26

12 12

8 8

40 29 17 1s

84

Cervical infection in pregnancy

Erythromycin 250 mg 4/day for Erythromycin SO0 mg 4/day for Erythromycin 500 mg 2/day for Erythromycin 250 mg 4/day for Other regimen Total

10 days 10 days 10 days 14 days

11

7

77 151

51 100

Probable pelvic infection

Lymecyclin 300 mg 2/day for 14 days Doxycyline 100 mg 2/day for 10 days Lymecycline 300 mg 2/day for 10 days Doxycylin 200 mg for 14 days Other Total

less than is recommended (Table IV). Probable pelvic infection would be ‘undertreated’ by more than 4 out of 10 GPs. Fifty GPs (29%) would add an imidazole to the regimen for pelvic infection. Logistic regression was performed on each diagnosis. The GPs who prescribed a regimen lcss than the recommended one were compared with the other GPs. The GPs background information were entered as independent variables. None of the variables had a significant influence o n the choice of regimen (data not shown).

Discussion More than 30% of the GPs did not answer the questionnaire, and this may result in a severe bias. However, one main conclusion stands firm: there is considerable variation in the management of genital chlamydial infection. This variation may be due to a great interest in chlamydial infection among the GPs. I rather belicve, however, that it reflects the contradictory advice the GPs receive on this topic. The manufacturer recommends a doxycycline regimen of 200 mg start, and thereafter 100-200 mg a day ( 3 ) . For erythromycin the manufacturer’s recommendation is 500 mg four times a day for ‘serious infections’ only (3). Actu Ob.strt Gynecol Scund 71 (1992)

19

11

17

I0 6 6 68 101

10 10 I19 175

A few GPs would even prescribe tetracyclines to pregnant patients. Hopefully, these answers were errors the GPs would not have commited in real life. I am convinced that the majority of Norwegian GPs would look up the prescription information regarding any drug they would prescribe to a pregnant woman. Only 151 of the 201 GPs who responded to the survey answered this question; perhaps indicating that many GPs were uncertain. The cost of the recommended regimens varies from f 5.1 to f 16. Doxycycline, the most expensive drug, is also the drug most frequently prescribed for non-pregnant patients. Fifty-eight percent of those GPs who prescribed doxycycline for cervicitis, prescribed one daily dose of 100 mg. GPs may hopc to achieve better patient compliance with an antibiotic that is taken only once a day. In the light of increasing emphasis on medical audit and the forthcoming Communicable Diseases Act, standardized treatment of chlamydial infections will be particularly relevant. Standardized treatment will secure all patients adequate treatment. Furthermore, it will save resources and reduce discomfort to patients by avoiding unnecessary treatments. Official guidelines would be the first step on the road to standardized treatment. C D C published their first guidelines on the treatment of chlamydia1 infections in 1982 (9). Sweden followed with their

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359

Table IV. Regimens used compared to recommended regimens Regimen

Compatible More* Less** Total

Cervical infection

Cervical infection in pregnancy

Probable pelvic infection

GPs using No.

%

GPs using No.

Y"

Gps using No.

Yo

26 68 91 185

14 37 49 I00

8 23 120 151

5 1.5 79 99

81 18 76 175

46 10 43 99

* One of the recommendcd antibiotics, but larger doses, more daily doses or longer duration than recommended * * Other antibiotic or recommended antibiotic in either smaller doses, fewer daily doses, shorter duration or combinations of these

guidelines in 1986 (lo), and Denmark with theirs in 1989 (11). The Swedish and Danish recommendations on doxycycline dosages are, however, not in accordance with the international guidelines. Both recommend 200 mg start followed by 100 mg daily. In addition, the Swedish guidelines recommend only half the tetracycline dose compared to the W H O , CDC and Danish guidelines. Finland and Norway have never proposed their own recommendations. A solution for these countries would be to implement the international guidelines. There are, however, some discrepancies in the international guidelines. Firstly, the Uppsala guidelines recommend lymecycline, a drug not even mentioned in the W H O or C D C guidelines. Secondly, the Uppsala guidelines recommend tetracycline 250 mg 4/day for 10 days, while CDC and W H O recommend 500 mg 4/day for 7 days. Thirdly, the Uppsala guidelines and MBrdh (12) advocate that all chlamydial cervicitides be treated as complicated infections, with a 10 - 14 days course of treatment. The argument is that a cervicitis and an endometritis are clinically indistinguishable. Furthermore, they point to the fact that approximately 40% of the cases of cervicitis are complicated by endometritis (13). In many cases, a 7 day course would, therefore, be inadequate. The cost-effectiveness of this strategy has yet to be defined. Norwegian official guidelines should not only be based on international guidelines, but should also address the problems mentioned here. The guidelines could be widely disseminated throughout the medical community, as well as throughout the medical schools and the regular postgraduate courses. The pharmaceutical industry should be encouraged to recommend the standard treatment for genital chlamydial infection in all their advertising. An effective means of standardizing treatment would be 25 *

through the reimbursement system of the new Communicable Diseases Act. It should be pointed out that this survey did not attempt to assess the efficacy of the different regimens used. Many of the regimens termed 'less than recommended' may be wholly adequate in terms of eradicating chlamydiae from the infected organs.

Conclusion In this survey I have found great variation in the antibiotic regimens prescribed in the treatment of genital chlamydial infections in women. More than 40% of these regimens are less than those recommended by international authorities. Implementation and dissemination of official guidelines are urgently needed.

References 1. Hasseltvedt V. Overvlking av seksuelt overforbare sykdornmer (SOS). MSIS Meldesyst infeksjonssykd . 1991; 19 (9) (In Norwegian). 2. Hasseltvedt V. OverViking av seksuelt overf0rbarc sykdommer (SOS). MSIS Meldesyst infeksjonssykd 1991; 19 (45) (In Norwegian). 3. Tgrisen HM, editor. Felleskatalog over farmas@ytiske spesialpreparater registrert i Norge. Oslo: I/S Farmainformasjon, 1991 (In Norwegian). 4. Centers for Discasc Control. 1989 Sexually Transmitted Diseases Treatment Guidelines. MMWR 1989; 38 (No. S-8): 27-33. 5 . WHO Technical Report Series 810. Management of patients with sexually transmitted diseases. Geneva: World Health Organization, 1991. 6. WHO Collaborating Centre for Sexually Transmitted Diseases and Their Complications. Guidelines for the prevention of genital chlamydial infections. Uppsala: University of Uppsala. 1991. Acta Obsrer

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7. Radcliffe KW, Rowen D, Mercey D E , Bingham JS. Survey of the management of Chlamydia truchomaris infection of the cervix. Genitourin Med 1991; 67: 41-3. 8. Centers for Disease Control. Pelvic inflammatory disease: guidelines for prevention and management. MMWR 1991; 40 (No. S-5): 15-17. 9. Centers for Disease Control. Sexually transmitted diseases treatment guidelines 1982. MMWR 1982; 31 (No. 2s): 35s-36s. 10. National Board of Health and Welfare Drug Information Committee. Treatment of sexually transmitted diseases. Uppsala: National Board of Health and Welfare, 1986. 11. Sundhedsstyrelsen. Vejledning for diagnose og behan-

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dling af seksuelt overforbare sygdomme. Kobenhavn: Sundhedsstyrelsen, 1989 (In Danish). 12. Mirdh P-A. Treatment of pelvic inflammatory disease and related matters [leading article]. J Antimicrob Chemother 1990; 25: 729-32. 13. Paavonen J, Kiviat N, Brunham RC et al. Prevalence and manifestations of endometritis among women with cervicitis. Am J Obstet Gynecol 1985; 152: 280-6.

Address for correspondence: Preben Aavitsland, M.D. National Institute of Public Health Geitmyrsveien 75 0462 Oslo Norway

Survey of the treatment of Chlamydia trachomatis infection of the female genital tract.

A questionnaire was sent to every tenth (n = 302) general practitioner in Norway. The physicians were to indicate their choice of antibiotic regimen f...
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